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Mechanistic Evaluation of Hydration Effects on the Human Epidermal Permeation of Salicylate Esters

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Abstract

We sought to understand when and how hydration enhances the percutaneous absorption of salicylate esters. Human epidermal membrane fluxes and stratum corneum solubilities of neat and diluted solutions of three esters were determined under hydrated and dehydrated conditions. Hydration doubled the human epidermal flux seen for methyl and ethyl salicylate under dehydrated conditions and increased the flux of neat glycol salicylate 10-fold. Mechanistic analyses showed that this hydration-induced enhancement arises mainly from an increase in the stratum corneum diffusivity of the three esters. Further, we showed that unlike methyl and ethyl salicylate, glycol salicylate is hygroscopic and the ∼10-fold hydration-induced flux enhancement seen with neat glycol salicylate may be due to its ability to hydrate the stratum corneum to a greater extent. The hydration-induced enhancements in in vitro epidermal flux seen here for glycol and ethyl salicylate were similar to those reported for their percutaneous absorption rates in a comparable in vivo study, whilst somewhat higher enhancement was seen for methyl salicylate in vivo. This may be explained by a physiologically induced self enhancement of neat methyl salicylate absorption in vivo which is not applicable in vitro.

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ACKNOWLEDGMENTS

This work was supported by grants from the National Health and Medical Research Council of Australia (APP1049906; 1002611). SY was supported by a scholarship from the Egyptian Government. We would like to thank Dr Eman Abd for helping with the CRM imaging. Our thanks go to Howard Maibach for helpful discussions and providing key references as well as to Croda International plc for the gift of chemical samples.

We thank Drs Xinyuan Zhang and Sam Raney from the FDA for their encouragement of this work which was funded in part by the Food and Drug Administration through grant U01FD005232. The views expressed in this publication do not reflect the official policies of the U.S. Food and Drug Administration or the U.S. Department of Health and Human Services; nor does any mention of trade names, commercial practices, or organization imply endorsement by the United States Government.

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Authors and Affiliations

  1. Therapeutics Research Centre, School of Medicine, University of Queensland, Translational Research Institute, Brisbane, Australia

    Shereen Yousef, Yousuf Mohammed, Sarika Namjoshi, Jeffrey Grice & Michael Roberts

  2. School of Pharmacy, Helwan University, Helwan, Egypt

    Shereen Yousef & Wedad Sakran

  3. School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia

    Michael Roberts

  4. Therapeutics Research Centre, The University of Queensland School of Medicine-Translational Research Institute, 37 Kent St, Woolloongabba, Brisbane, QLD, 4102, Australia

    Michael Roberts

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  1. Shereen Yousef
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Correspondence to Michael Roberts.

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Yousef, S., Mohammed, Y., Namjoshi, S. et al. Mechanistic Evaluation of Hydration Effects on the Human Epidermal Permeation of Salicylate Esters. AAPS J 19, 180–190 (2017). https://doi.org/10.1208/s12248-016-9984-0

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